title: Association of peripheral CD4+ CXCR5+ T cells with chronic lymphocytic leukemia.
abstract: Accumulating evidences indicate that immune dysregulation plays a key role in both lymphomagenesis and patient outcome of chronic lymphocytic leukemia (CLL). Peripheral blood CD4+ CXCR5+ T cells, known as circulating follicular helper T cells (Tfh), can induce B cell activation and production of specific antibody responses. The aim of the study was to investigate changes of circulating Tfh in CLL. Tfh and it subtypes were tested by measuring CD4, CXCR5, CXCR3, and CCR6 in 72 CLL cases and 86 healthy controls using flow cytometry. Data showed that the percentage of Tfh in the peripheral CD4+ T cells was significantly increased in CLL (25.1%) than in controls (8.4%) (p < 0.001). Further analysis revealed that the upregulation of Tfh was contributed by Tfh-th2 subtype and Tfh-th17 subtype. Investigating staging of the cases demonstrated that the prevalence of Tfh was significantly elevated in cases with Binet stage C (37.3%) than those with stage A (20.1 %) or stage B (23.9 %). In addition, we analyzed Tfh in patients with immunoglobulin variable heavy chain (IGHV) gene mutational status. Results presented that Tfh-th17 subtype had clearly higher frequency in patients with IGHV mutation compared to the unmutated cases (p = 0.035). This study suggested the involvement of Tfh in the pathogenesis and progression of CLL, and provided a potential target for treating this disease.
authors.affiliation: Department of Transfusion, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai, 200433, China.
authors.forename: Zhanshan
authors.initials: Z
authors.lastname: Cha
authors.forename: Yan
authors.initials: Y
authors.lastname: Zang
authors.forename: Huijun
authors.initials: H
authors.lastname: Guo
authors.forename: James R
authors.initials: JR
authors.lastname: Rechlic
authors.forename: Lindsay M
authors.initials: LM
authors.lastname: Olasnova
authors.forename: Haihui
authors.initials: H
authors.lastname: Gu
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Tu
authors.forename: Haihan
authors.initials: H
authors.lastname: Song
authors.forename: Baohua
authors.initials: B
authors.lastname: Qian
mesh_terms: D000328:Adult; D000368:Aged; D015704:CD4 Antigens / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D004252:DNA Mutational Analysis; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D054399:Receptors, CCR6 / Q000276:immunology / Q000378:metabolism; D054367:Receptors, CXCR3 / Q000276:immunology / Q000378:metabolism; D054380:Receptors, CXCR5 / Q000276:immunology* / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism
chemical_list: C106311:CCR6 protein, human; D015704:CD4 Antigens; C515187:CXCR3 protein, human; C095085:CXCR5 protein, human; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D054399:Receptors, CCR6; D054367:Receptors, CXCR3; D054380:Receptors, CXCR5